Numerous types of vascular and musculoskeletal grail substitutes have been produced in the last four decades. Vascular graft substitutes have included large and small diameter vascular, blood carrying tubular structures, grafts containing valvular structures (vein substitutes, and heart valve substitutes) and those lacking valvular structures (artery substitutes). The materials out of which these vascular grafts have been constructed have included man-made polymers, notably Dacron and Teflon in both knitted and woven configurations, and non-man-made polymers, notably tissue engineered blood vessels such as described in U.S. Pat. Nos. 4,539,716, 4,546,500, 4,835,102; blood vessels derived from animal or human donors such as described in U.S. Pat. Nos. 4,776,853, 5,558,875, 5,855,617, 5,843,181, and 5,843,180; and connective tissue grafts as described in U.S. Patent Application No. 2001/0000804 and U.S. Pat. Nos. 6,267,786, 5,865,849, 5,902,338, 5,922,027, 5,944,755, 5,984,858, 4,801,299, and 4,776,853.
The prior art processing methods are directed to decellularizing tissue grafts, i.e. removing all cellular elements, leaving a tissue matrix free from cellular elements, and are prohibitively time consuming, easily requiring numerous days, for example anywhere from eight to twenty-one days total processing time. Such long processing times result in proteolytic degradation of the matrix structures of the processed tissues and may result in the accumulation of residuals from the various processing solutions. Over the past few decades numerous efforts have been made to manage the large demand for vascular prostheses in the treatment of vascular dysfunctions/pathologies and musculoskeletal prostheses in the treatment of orthopedic dysfunctions/pathologies. While vascular prostheses are available for clinical use, they have met with limited success due to cellular and immunological complications, and the inability to remain patent and functional. These problems are especially pronounced for small diameter prostheses, i.e. less than about 6 mm. Efforts have been directed at removing those aspects of allograft and xenograft vascular prostheses that contribute to immunological “rejection” and these efforts have focused primarily on the development of various “decellularization” processes, which require unduly burdensome incubation times and vast numbers of reagents. In addition, the methods used in the prior art dictate the use of large volumes of processing solutions which do not lend themselves to the production of acellular grafts on a commercializable scale.